LINE-1 hypomethylation and mutational status in cutaneous melanomas

Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss of DNA methylation in gene-poor regions and transposable DNA elements of cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the mos...

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Bibliographic Details
Published in:Journal of investigative medicine 2016-04, Vol.64 (4), p.899-904
Main Authors: Pramio, Dimitrius T, Pennacchi, Paula C, Maria-Engler, Silvya S, Campos, Antônio H J F M, Duprat, João P, Carraro, Dirce M, Krepischi, Ana C V
Format: Article
Language:English
Subjects:
Cell cycle
Committees
Deoxyribonucleic acid
DNA
DNA methylation
DNA Methylation - genetics
DNA Mutational Analysis
Epigenetics
Gene expression
Genetic testing
Genomes
Humans
Kinases
Long Interspersed Nucleotide Elements - genetics
Medical prognosis
Melanoma
Melanoma - genetics
Melanoma, Cutaneous Malignant
Metastasis
Mutation
Mutation - genetics
Prostate
Skin cancer
Skin Neoplasms
Studies
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Summary:Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss of DNA methylation in gene-poor regions and transposable DNA elements of cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the most abundant repetitive sequence of the genome and can be evaluated as a surrogate marker of the global level of DNA methylation. In this work, LINE-1 methylation levels were evaluated in cutaneous melanomas and normal melanocyte primary cell cultures to investigate their possible association with both distinct clinicopathological characteristics and tumor mutational profile. A set of driver mutations frequently identified in cutaneous melanoma was assessed by sequencing (actionable mutations in BRAF, NRAS, and KIT genes, and mutations affecting the TERT promoter) or multiplex ligation-dependent probe amplification (MLPA) (CDKN2A deletions). Pyrosequencing was performed to investigate the methylation level of LINE-1 and CDKN2A promoter sequences. The qualitative analysis showed a trend toward an association between LINE-1 hypomethylation and CDKN2A inactivation (p=0.05). In a quantitative approach, primary tumors, mainly the thicker ones (>4 mm), exhibited a trend toward LINE-1 hypomethylation when compared with control melanocytes. To date, this is the first study reporting in cutaneous melanomas a possible link between the dysregulation of LINE-1 methylation and the presence of driver mutations.
ISSN:1081-5589
1708-8267
DOI:10.1136/jim-2016-000066